Dynamin-mediated endocytic process contributes to neuronal nitric oxide synthase-mediated regulation of cardiac contraction / 生理学报

ABSTRACT

Nitric oxide synthases (NOSs) play complex roles in the regulation of cardiac excitation contraction coupling under basal and stressed conditions. Herein, using the recording approach for intracellular calcium transient and synchronous myocyte contraction, the potential mechanism for NOSs-mediated cardiomyocyte contraction was explored. We found that selective inhibition of neuronal NOS (nNOS) with 100 µmol/L spermidine markedly enhanced the cardiomyocyte twitch [control (10.5 ± 0.21)%; nNOS inhibition (12.4 ± 0.18)%] and calcium transient [control (0.27 ± 0.03)%; nNOS inhibition (0.42 ± 0.01)%], but slowed the relengthening of twitch [control (25.2 ± 1.3) ms; nNOS inhibition (53 ± 2.8) ms] and the calcium transient decay [control (129 ± 4.3) ms; nNOS inhibition (176 ± 7.1) ms], which was similar to that by dynamin inhibition with 30 µmol/L dynasore. The nNOS inhibition- or dynasore-mediated effects could be rescued by an NO donor, S-Nitroso-N-acetylpenicillamine (SNAP). Our data suggest that the selective nNOS-mediated regulation of cardiac contractile activity may partly involve the dynamin-mediated endocytic mechanism.